OMEGA-CONOTOXIN GVIA IS A POTENT INHIBITOR OF SYMPATHETIC NEUROGENIC RESPONSES IN RAT SMALL MESENTERIC-ARTERIES

1. We have investigated the effects of the N-type calcium channel blocker, ω-conotoxin GVIA, on contractile responses to nerve stimulation, noradrenaline and KCl in rat small mesenteric arteries. In separate experiments, single and summated excitatory junctional potentials (e.j.ps) evoked by nerve stimulation were recorded with an intracellular electrode in the absence and presence of ω-conotoxin. 2. Electrical field stimulation of intramural sympathetic nerves (30 V; 0.25 ms pulse width; 3 s train length; 4-24 Hz) caused frequency-dependent contractions. Cumulative concentration-response curves for the contractions induced by noradrenaline and KCl were constructed in the same preparations. Stimulation at 0.2 Hz and 10 Hz induced respectively single e.j.ps without contractions and summated e.j.ps associated with a contractile response. 3. ω-Conotoxin (0.1 to 3 nM) inhibited markedly and in a concentration-dependent manner both the contractions and e.j.ps to electrical field stimulation. The concentration-response curves to exogenous noradrenaline and KCl remained unaffected. 4. The time-course for the effects of ω-conotoxin (0.3 to 3 nM) indicated a slow onset of action with at least one hour to achieve an equilibrium. 5. The experiments indicate that ω-conotoxin acts prejunctionally to inhibit sympathetic neurotransmission in rat small arteries presumably by inhibition of noradrenaline release. We suggest that ω-conotoxin could be a useful tool to study the control of vascular tone through the autonomic nervous system.